Genomics

Dataset Information

300

Prep1 and Meis1 competition for Pbx1 binding regulates protein stability and tumorigenesis [hP]


ABSTRACT: Prep1 is a tumor-suppressor, whereas Meis1 is an oncogene. We show that to perform these activities in MEFs both proteins competitively hetero-dimerize with Pbx1. Meis1 alone transforms Prep1-deficient fibroblasts while Prep1 overexpression inhibits Meis1 tumorigenicity. Pbx1 can therefore alternatively act as oncogene or tumor-suppressor. Prep1 post-translationally controls the level of Meis1 decreasing its stability by sequestering Pbx1. The different levels of Meis1 and the presence of Prep1 are followed at the transcriptional level by the induction of specific transcriptional signatures. The decrease of Meis1 prevents Meis1 interaction with Ddx3x and Ddx5, which are essential for Meis1 tumorigenesis, and modifies the growth promoting DNA binding landscape of Meis1 to the growth controlling landscape of Prep1. Hence the key feature of Prep1 tumor inhibiting activity is the control of Meis1 stability. Examination of Prep1 and Meis1 in two cell types

ORGANISM(S): Mus musculus  

SUBMITTER: Leila Dardaei   Francesco Blasi 

PROVIDER: E-GEOD-58802 | ArrayExpress | 2016-06-01

SECONDARY ACCESSION(S): GSE58802SRP043551PRJNA253530

REPOSITORIES: GEO, ArrayExpress, ENA

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Publications

Prep1 and Meis1 competition for Pbx1 binding regulates protein stability and tumorigenesis.

Dardaei Leila L   Longobardi Elena E   Blasi Francesco F  

Proceedings of the National Academy of Sciences of the United States of America 20140227 10


Pbx-regulating protein-1 (Prep1) is a tumor suppressor, whereas myeloid ecotropic viral integration site-1 (Meis1) is an oncogene. We show that, to perform these activities in mouse embryonic fibroblasts, both proteins competitively heterodimerize with pre-B-cell leukemia homeobox-1 (Pbx1). Meis1 alone transforms Prep1-deficient fibroblasts, whereas Prep1 overexpression inhibits Meis1 tumorigenicity. Pbx1 can, therefore, alternatively act as an oncogene or tumor suppressor. Prep1 posttranslation  ...[more]

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